Psilocybin compositions

ABSTRACT

Methods and compositions are disclosed for enhancing neurogenesis, resolving neuropathy and improving neurological health and functioning using fungal extracts and their active ingredients, including species of mushrooms and mycelia containing psilocybin and psilocin, combined with erinacines and hericenones or fungal extracts containing those active ingredients, with the addition of nicotinic acid. The compositions may optionally be combined with nervine plants.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/494,503, filed Apr. 23, 2017 which claims priority to U.S.Provisional Patent Application No. 62/365,982, filed Jul. 23, 2016, eachof which is hereby incorporated by reference in its entirety.

BACKGROUND

The present invention relates to neuroregenerative compositions basedupon constituents isolated from or contained within mushroom fruitbodiesor mycelia, or the corresponding synthetic molecules, combined withniacin.

BRIEF SUMMARY

The current invention describes novel contributions to the field ofmedicinal mushroom research, particularly discoveries pertaining toneuroregeneration.

The tragedy of aging is the loss of accumulated knowledge due toneuropathy, especially related to dementia, Alzheimer's, and otherneurological disorders. The cause of these disorders is a matter ofdispute, ranging from free radical damage to exposure to toxins toinability of neurons to regenerate in the numbers and quality necessaryfor healthy mental functioning. In addressing a disease complex withmultifactorial causes, offering a combination of elements that cansynergistically repair and improve neurological function is an importantstep in helping cognitive and motor skills, in particular, as humans ageand/or when exposed to neurotoxins, stress or head trauma. Not only arebenefits realized from multiple active principle ingredients activatingneurogenesis, but the compositions and methods below may additionallyhelp mitigate and/or reverse ocular and cochlear nerve degeneration.

A composition including psilocybin(4-phosphoryloxy-N,N-dimethyltryptamine) or psilocin(4-hydroxy-N,N-dimethyltryptamine) in pure form or extracts fromPsilocybe and psilocybin containing mushrooms combined with erinacinesor hericenones, or extracts from Hericium mushroom species, and niacin(nicotinic acid or 3-pyridinecarboxylic acid, also known as vitamin B3),uniquely aids in repairing and improving neurologic functioning andsignaling. Schartner et al. (2017) reported substantial increased globalneural signal diversity in a psilocybin-human clinical study (NatureScientific Reports, 7:46421). Additionally, niacin is known to be aneural anti-inflammatory, and, in itself, has been implicated inimproving neural functioning. As niacin activates nerve endings, theinventor suggests that the addition of niacin contributes an addedbenefit by enhancing the neurogenic effects of psilocybin, psilocin,erinacines and hericenones by helping these nootropics cross the bloodbrain barrier, and migrate throughout the nervous systems, and to itsend points. Moreover, niacin is a vasodilator improving blood flow inthe brain by relaxing constricted blood vessels. This unique combinationnot only rebuilds myelin upon the axons, it also activates newastrocyte/astroglial cells and neuronalnodes of crossings such as thesynaptic regions, particularly in the hippocampus. Other medicinalmushroom species also can be added, particularly species of Antrodia,Beauvena, Copelandia, Cordyceps, Ganoderma, Grifola, Inonotus, Isana,Panaeolus, Phellinus, and other medicinal mushrooms and their myceliawhose unique neurogenerative properties may add benefits to this basicformulation. An excellent summary of the prior art related to the use ofmushrooms as “brain foods” can be found in Phan et al. (2017), “Edibleand Medicinal Mushrooms: Emerging Brain Food for the Mitigation ofNeurodegenerative Diseases,” Journal of Medicinal Foods 20(1): 1-10.Lion's Mane (Hericium erinaceus), Bear's Head (H. coralloides), or CombTooth (H. ramosum) mushrooms and mycelium have also been well studiedand reported to regenerate myelin on the axons of nerves. Two particularfamilies of compounds are most noteworthy—erinacines and hericenones.Erinacines, including known erinacines A-K, P and Q, are cyanthaneterpenes isolated from the mycelia of Hericium erinaceus that promoteNGF (nerve growth factor) synthesis. Hericenones, including knownhericenones C-H, are cyanthane terpenes located in both the mycelia andfruiting body of Hericium erinaceus that promote NGF synthesis. Friedmanet al. (2015) summarizes these activities in “Chemistry, Nutrition, andHealth-Promoting Properties of Hericium ennaceus (Lion's Mane) MushroomFruiting Bodies and Mycelia and Their Bioactive Compounds,” Journal ofAgricultural and Food Chemistry 63: 7108-7123.

Although Phan et al. describes many species with potentialneurogenerative properties, the psilocybin or psilocybian species (i.e.“psilocybin-containing”, from the use of “psilocybienne” as described bythe French mycologist, Roger Heim, with R. Gordon Wasson, in 1957 in Leschampignons hallucinogene du mexique. Paris: Museum de historienaturelle; 1958, pp. 268-71) are not mentioned, either alone or incombinations with the edible and medicinal mushroom species described byPhan. A good summary of the role of psilocybin in humans can be found inPassie et al. (2002), “The Pharmacology of Psilocybin,” AddictionBiology 7: 357-364. That psilocybin has neurogenerative properties waselucidated by Catlow et al. (2013), “Effects of psilocybin onhippocampal neurogenesis and extinction of trace fear conditioning,”Experimental Brain Research 228: 481-491.

The present nootropic invention can benefit those suffering from age ortrauma related neuropathologies including but not limited to tinnitus,organophosphates and other toxic compounds), heavy metals, prions,amyloid plaque formation, demyelination, nerve signaling, neurotoxicviruses, stress and numerous other agents causing neuropathies.Psilocybian mushrooms, their enzymes and their indole alkaloids maycounteract and reduce the toxicity of methyl phosphonates—the corestructure of Sarin, a potent neurotoxin, used in nerve gases. Moreover,the use of psilocin and psilocybin in the compositions described heremay help block the neurotoxicity effects of chemical nerve toxins andlead to protecting and healing military and civilians exposed to sarinand other neurotoxic agents. The use of fungal extracts also potentiallyenables neurogenesis by removing agents harmful to neurological health,including but not limited to parasites such as nematodes, protozoa,pathogenic bacteria, including Borrelia species and other spirochetes,and other infectious organisms or viruses. The benefits of thisinvention to the nervous system is hard to overstate. Additionalbenefits are conferred not only to humans challenged with diseases orneurotoxins, but also in healthy humans, including but not limited toincreased cognitive function in students, scientists, computer coders,hackers, Big Data specialists, mathematicians, astronomers, strategicplanners (i.e. such as in the U.S. Defense Department), gamers,linguists, writers, futurists, Mensa members, athletes, soldiers,religious leaders, politicians, business leaders or anyone benefittingfrom increased memory, intelligence, imagination, cognition,clairvoyance, motor skills, spatial navigation, athleticism, ability tomore quickly respond to and process stimuli, balance, neuroplasticity,state of mind, longevity and mental health. Various benefits are alsoexpected in vertebrate animals including mammals, carnivores, omnivores,herbivores, pets including cats and dogs and companion animals, farm andproduce animals, laboratory animals, zoo animals, reptiles, fish andbirds. The compounds of the present invention may also be useful forbees, including those suffering from pesticides, viruses or at risk fromColony Collapse Disorder, and various other invertebrates.

DETAILED DESCRIPTION

Niacin (nicotinic acid) has long been reported to counteract the effectsof psilocybin and LSD, helping those experiencing adverse reactions or“bad trips” to return to a non-psychoactive state of mind, by reversingthe excitement of nerve receptors. Therefore, the prior art teaches awayfrom using niacin to excite nerve endings using psilocybin or psilocin.Hence, counter-intuitively, this invention uniquely combines niacin withpsilocin/psilocybin and erinacines/hericenones for neurologicalrestructuring and improved neurological health. By adding niacin into apsilocybin-centered neuroregenerative nootropic nutraceutical, vitamincomplex or medicine in sufficient quantities to cause extreme discomfortfor those who might try to abuse a therapeutic combination containingpsilocin or psilocybin, this invention provides improved methods andcompositions to prevent potential abuse by those wishing to get “high.”Analogous to effects of Antabuse (disulfiram), which induces anunpleasant experience for those abusing alcohol, the addition ofsufficient quantities of niacin, which likewise causes extremediscomfort, with psilocybin/psilocin will help prevent the abuse of thedescribed neurogenic formulas.

As little as 10-35 mg per day of niacin causes flushing redness on theskin, itchiness, burning and unpleasant tingling. Higher doses can leadto liver damage. 500 mg. per day is considered the top tier for safe useunless prescribed by a physician who closely monitors the patient foradverse effects. Some cholesterol-lowering products contain up to 500milligrams of niacin and these levels can interfere with the metabolismof other medicines. 3,000 milligrams per day is clearly toxic. Uponhydrolysis, a drug called Picamilon produces GABA and niacin, allowingthe inhibitory neurotransmitter GABA to pass through the blood-brainbarrier. The addition of niacin to GABA to form nicotinyl-γ-aminobutyricacid or N-nicotinoyl-GABA also aids the passage of GABA across theblood-brain barrier. The stacking of niacin, psilocybin (or psilocin),GABA, erinacines and hericenones is an additional embodiment of thisinvention. Further embodiments include the addition of vanillic acid,trans-ferulic acid, trans-cinnamic acid, or other antiviral,anti-inflammatory polyphenols to reverse neuropathies, especially inthose harmed by viruses such as, but not limited to, herpes simplexviruses (HSV), human papilloma viruses (HPV), polio, pox and otherneurotoxic and inflammatory viruses.

Moreover by using psilocin or psilocybin at levels equivalent to what iscolloquially known as “microdoses,” i.e. <1 mg per day for a 70 kgindividual, compounding effects can be realized over time. Such lowdoses have no noticeable consciousness altering effects on the personingesting, and moreover, it is well know that tolerance to any perceivedeffects in altering one's consciousness is achieved very quickly fromdaily dosing of even higher levels, such as 10 mg of psilocin orpsilocybin per day for a 70 kg person. Johns Hopkins researchers foundthe “sweet spot” for full-blown therapeutic doses to be around 35 mg ofpsilocybin/psilocin for a 70 kg person. (Note that psilocybin isdephosphorylated into psilocin, which passes through the blood-brainbarrier.)

The term “effective amount” or “therapeutic amount” refers to an amountsufficient to have neurogenerative activity. This amount may vary tosome degree depending on the mode of administration, but will be in thesame general range. The exact effective amount necessary could vary fromsubject to subject, depending on the compound, preventative treatment orcondition

10 being treated, the mode of administration, etc. The appropriateeffective amount may be determined by one of ordinary skill in the artusing only routine experimentation or prior knowledge in the art in viewof the present disclosure. Note that effective ranges/dosages are notexpected to be precisely the same for all compounds. Dosages may beoptimized with each compound when the pharmacokinetics are studied tosee how each compound is metabolized, which may alter the dose ranges.Nevertheless, given these factors, this neuro-enhancing invention isbest managed in consultation with a skilled medical professional.

A suggested formula containing optional nervine plants that serves thepurpose of neurological benefit but below any noticeable level ofintoxication could be a 550 mg delivery dose via an ingestible capsuleor by any means known to the art of drug delivery:

Neurogenesis Formula 1 Psilocin or psilocybin 1 mg Erinacines orhericenones 50 mg Niacin per day 200 mg Extract of Hericium erinaceus,199 mg H. corralloides, H. abietis mycelium and/or fruitbodies ofmedicinal mushrooms Extracts of plants with neurogenic properties* 100mg

Plant extracts with known neuroregenerative properties include, but arenot limited to: Bacopa species (Bacopa monnien), Gotu kola (Centellaasiatica), and Gingko (Gingko biloba). Additional plants withanti-inflammatory properties include but are not limited to: Ginger(Zingiber officinals), Holy Basil (Ocimum sanctum), Hu Zhang (Polygonumcuspidatum), Oregano (Origanum vulgare, Origanum onites), Rosemary(Rosmarinus officinalis, Rosmarinus eriocalyx, species in the genusRosmarinus), Turmeric (Curcuma longa), Green Tea (Camellia sinensis),lavender (Lavandula spica and related species in the genus Lavandula),skullcap (Scutellaria lateriflora) and oat straw (Avena sativa, Avenabyzantina). Moreover, Salvia divinorum, aka Diviner's Sage, ayahuasca, aconcoction made from Banisteriopsis caapi and Psychotna species, andplants containing ibogaine (Tabemanthe iboga, Voacanga africana andTabemaemontana undulate), peyote (Lophophora williamsil), the seeds ofmorning glory (Ipomoea tricolor and related species) and Hawaiian babywoodrose (Argyreia nervosa), and Cannabis (Cannabis sativa, C. indicaand C. ruderalis), can be incorporated as well. Any nervine agents fromnatural products may also be incorporated, including, for example,cordycepin (or Cordyceps extracts containing such) or amyloban (found inLion's mane).

Depending on individual factors such as variations in metabolism,neurotransmitters and preventative treatment or condition, such aregimen of 500-1000 mg. of intake once to three times daily may producemeasurable effects in one year, or the regimen may extend for up to ayear or more before noticeable neurological benefits are evident. Sincepsilocybin converts to psilocin and is typically not detectable in theurine in 24 hours, the long term use of this nootropic formulationsustains psilocin as a serotonin agonist, while not activating dopaminereceptors.

In another embodiment, the composition comprises one or more of ethyl7-chloro-2-oxo-4-phenyl-2H-chromen-3-carboxylate, vanillic acid,chrysin, quercetin hydrate, rutin hydrate, syringic acid, trans-cinnamicacid, trans-ferulic acid, salts thereof, esters thereof, or combinationsthereof, and thereby has an antiviral effect against a pathogenic viruscomprising one or more of herpes Varicella zoster virus, Epstein-Barrvirus, herpes simplex I and II viruses, human papillomaviruses (HPV),poliovirus, or viruses which contribute to neuropathies.

As ranges of these active ingredients can vary, the inventor anticipatesthe ranges giving benefits will include:

Neurogenesis Formula 2 (based on a 70 kg, 154 lb person) Psilocin orpsilocybin 0.1 mg to 0.6 mg Erinacines or hericenones 1 mg to 20 mgNiacin per day 1 to 50 mg Neurogenesis Formula 3 Psilocin or psilocybin0.6 mg to 0.9 mg Erinacines or hericenones 20 mg to 50 mg Niacin per day50 mg to 100 mg Neurogenesis Formula 4 Psilocin 0.9 mg to 10 mgErinacines or hericenones 50 mg to 200 mg Niacin per day 100 mg to 200mg Neurogenesis Formula 5 Psilocin or psilocybin 0.1 mg to 10 mgErinacines or hericenones 1 mg to 200 mg Niacin per day 1 mg to 200 mgNeurogenesis Formula 6 Psilocin or psilocybin 1 mg to 10 mg Erinacinesor hericenones 50 mg to 200 mg Niacin per day 101 mg to 200 mgNeurogenesis Formula 7 Psilocybin mushroom @ 1% psilocin or psilocybin0.1 g to 1 g Lion's mane mushroom @ 1% erinacines or 50 mg to 200 mghericenones Niacin per day 101 mg to 200 mg

Compounds naturally produced by the mycelium of psilocybian mushroomsand their mycelium includes baeocystin, norbaeocystin,N,N-dimethyltryptamine, 5-hydroxytryptamine (serotonin),5-hydroxytryptophan, psilocybin and psilocin. These compounds, theirprecursors and immediate derivatives are candidates for neurogenesis.Synthetic or natural prodrugs, congeners and analogs of psilocybin,psilocin, baeocystin and norbaeocystin may offer similar benefits.Congeners are chemical substances related to each other by origin,structure, or function. Analogs (or analogues or structural analogs) arecompounds having a structure similar to another, but differing from itin respect of a certain substituent in which one or more atoms orfunctional groups which are replaced with other atoms or groups orsubstituents. Psilocybin and psilocin prodrugs and analogs that maysimilarly prove useful include those where the hydroxyl group ismodified or the methyl groups of the terminal amine nitrogen have beenmodified. Example hydroxyl group substituents include alkyl and arylethers and esters, for example methoxy and ethoxy ethers and acetylesters, halogens including fluoro-, chloro- and bromo-substituents, andthio groups such as methylthio or benzothio. Example nitrogen groupsubstituents include one or both methyl groups substituted with ethyl,propyl, isopropyl, butyl, isobutyl, secbutyl, tertbutyl, amyl or allylgroups and the N-trimethyl analogs. The corresponding phosphate esters,namely psilocybin and baeocystin analogs, may also prove useful, as mayanalogs where one or more hydrogen atom is replaced by fluorine,chlorine or bromine. Also preferred, where possible, are the salts ofthe tryptamine compounds, for example hydrochloride, fumarate, maleate,picrate, oxalate, tartrate and sulfate salts, which are typically morestable. Also preferred are the zwitterionic forms, particularly of thephosphate esters and quaternary ammonium compounds. Preferred analogsinclude: 4-acetoxy-N,N-dimethyltryptamine (4-AcO-DMT orO-Acetylpsilocin) the acetylated form of the psilocin (4-OH-DMT). It isa possible prodrug of psilocin (as are other 4-alkyl-esters), morestable than psilocin, and has a longer shelf life;4-acetoxy-N-methyl-N-ethyltryptamine (4-AcO-MET), a psilocin analogsubstituted at R4 of its indole heterocycle with an acetoxy (AcO orCH₃COO⁻) functional group which also contains a methyl group and anethyl chain bound to the terminal amine nitrogen of its tryptaminebackbone. 4-AcO-MET is an acetate ester analog of 4-OH-MET and aN-substituted ethyl homolog of 4-AcO-DMT;4-acetoxy-N,N-diethyltryptamine(4-AcO-DET);4-acetoxy-N-methyl-N-propyltryptamine (4-AcO-MPT);4-acetoxy-N-methyl-N-isopropyltryptamine (4-AcO-MIPT);4-acetoxy-N,N-dipropyltryptamine (4-AcO-DPT) and4-acetoxy-N,N-diisopropyltryptamine (4-AcO-DI PT);4-hydroxy-N-methyl-N-ethyltryptamine (4-OH-MET, metocin or methylcybin),a 4-hydroxy N-substituted structural analog of psilocin and the with amethyl and an ethyl group bound to the terminal amine nitrogen of thetryptamine structure; 4-hydroxy-N-methyl-N-propyltryptamine(4-OH-MPT);4-hydroxy-N-methyl-N-isopropyltryptamine (4-OH-MI PT);4-hydroxy-N,N-diethyltryptamine(4-OH-DET);4-hydroxy-N,N-dipropyltryptamine(4-OH-DPT);4-hydroxy-N,N-diisopropyltryptamine (4-OH-DI PT); and4-hydroxy-N,N-diallyltryptamine (4-OH-DALT); analogs where the 4-OHgroup has been removed, such as N,N-dimethyltryptamine (DMT),N-methyl-N-ethyltryptamine (MET), N-methyl-N-propyltryptamine (MPT),N,N-diethyltryptamine (DET), N,N-dipropyltriptamine (DPT),N,N-iisopropyltryptamine (DIPT), N-methyl-N-isopropyltryptamine (MIPT),a-methyl-tryptamine (AMT), N-ethyl-N-isopropyltryptamine (EIPT),N-methyl-N-butyl-tryptamine (MBT) or analogs substituted at otherpositions such as N,N-dimethyl-5-hydroxytryptamine (5-OH-DMT orbufotenine), 5-methoxy-a-methyltryptamine (5-MeO-aMT),5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT),5-methoxy-N,N-diethyltryptamine (5-MeO-DET),5-methoxy-N,N-dipropyltryptamine (5-MeO-DPT),5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT),5-methoxy-N-ethyl-N-isopropyltryptamine (5-MeO-EIPT),2,a-dimethyltryptamine (2,a-DMT), a,N-dimethyltryptamine (a,N-DMT),a-ethyltryptamine (a-ET), 2-methyl-N, N-dimethyltryptamine (2-Me-DMT),2-methyl-N, N-diethyltryptamine (2-Me-DET), 1-methylpsilocin andibogaine (a complex tryptamine). In general, equimolar amounts of ananalog may be used in place of psilocybin and/or psilocin in theformulas above, or amounts producing equivalent functional effects maybe utilized. See TiHKAL: The Continuation by Alexander Shulgin and AnnShulgin (1997, Transform Press) for an in-depth discussion of both“legal” analogs and “chemical” analogs, and synthesis and effects ofvarious psilocybin and psilocin analogs.

Additional pharmaceutical excipients useful for the compositions asdescribed herein include, for example, the following: acidifying agents(acetic acid, glacial acetic acid, citric acid, fumaric acid,hydrochloric acid, diluted hydrochloric acid, malic acid, nitric acid,phosphoric acid, diluted phosphoric acid, sulfuric acid, tartaric acid);alkalizing agents (ammonia solution, ammonium carbonate, diethanolamine,diisopropanolamine, potassium hydroxide, sodium bicarbonate, sodiumborate, sodium carbonate, sodium hydroxide, trolamine); antifoamingagents (dimethicone, simethicone); antimicrobial preservatives(benzalkonium chloride, benzalkonium chloride solution, benzethoniumchloride, benzoic acid, benzyl alcohol, butylparaben, cetylpyridiniumchloride, chlorobutanol, chlorocresol, cresol, dehydroacetic acid,ethylparaben, methylparaben, methylparaben sodium, phenol, phenylethylalcohol, phenylmercuric acetate, phenylmercuric nitrate, potassiumbenzoate, potassium sorbate, propylparaben, propylparaben sodium, sodiumbenzoate, sodium dehydroacetate, sodium propionate, asorbic acid,thimerosal, thymol); antioxidants (ascorbic acid, ascorbyl palmitate,butylated hydroxyanisole, butylated hydroxytoluene, hypophosphorousacid, monothioglycerol, propyl gallate, sodium formaldehyde sulfoxylate,sodium metabisulfite, sodium thiosulfate, sulfur dioxide, tocopherol,tocopherols excipient); buffering agents (acetic acid, ammoniumcarbonate, ammonium phosphate, boric acid, citric acid, lactic acid,phosphoric acid, potassium citrate, potassium metaphosphate, potassiumphosphate monobasic, sodium acetate, sodium citrate, sodium lactatesolution, dibasic sodium phosphate, monobasic sodium phosphate);chelating agents (edetate disodium, ethylenediaminetetraacetic acid andsalts, edetic acid); coating agents (sodium carboxymethylcellulose,cellulose acetate, cellulose acetate phthalate, ethylcellulose, gelatin,pharmaceutical glaze, hydroxypropyl cellulose, hydroxypropylmethylcellulose, hydroxypropyl methylcellulose phthalate, methacrylicacid copolymer, methylcellulose, polyvinyl acetate phthalate, shellac,sucrose, titanium dioxide, carnauba wax, microcrystalline wax, zein);colorants (caramel, red, yellow, black or blends, ferric oxide);complexing agents (ethylenediaminetetraacetic acid and salts (EDTA),edetic acid, gentisic acid ethanolamide, oxyquinoline sulfate);desiccants (calcium chloride, calcium sulfate, silicon dioxide);emulsifying and/or solubilizing agents (acacia, cholesterol,diethanolamine (adjunct), glyceryl monostearate, lanolin alcohols, mono-and di-glycerides, monoethanolamine (adjunct), lecithin, oleic acid(adjunct), oleyl alcohol (stabilizer), poloxamer, polyoxyethylene 50stearate, polyoxyl 35 castor oil, polyoxyl 40 hydrogenated castor oil,polyoxyl 10 oleyl ether, polyoxyl 20 cetostearyl ether, polyoxyl 40stearate, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate80, diacetate, monostearate, sodium lauryl sulfate, sodium stearate,sorbitan monolaurate, sorbitan monooleate, sorbitan monopalmitate,sorbitan monostearate, stearic acid, trolamine, emulsifying wax);filtering aids (powdered cellulose, purified siliceous earth); flavorsand perfumes (anethole, benzaldehyde, ethyl vanillin, menthol, methylsalicylate, monosodium glutamate, orange flower oil, peppermint,peppermint oil, peppermint spirit, rose oil, stronger rose water,thymol, tolu balsam tincture, vanilla, vanilla tincture, vanillin);humectants (glycerol, hexylene glycol, sorbitol); plasticizers (e.g.,castor oil, diacetylated monoglycerides, diethyl phthalate, glycerol,mono- and di-acetylated monoglycerides, propylene glycol, triacetin,triethyl citrate); polymers (e.g., cellulose acetate, alkyl celluloses,hydroxyalkyl, acrylic polymers and copolymers); solvents (acetone,alcohol, diluted alcohol, amylene hydrate, benzyl benzoate, butylalcohol, carbon tetrachloride, chloroform, corn oil, cottonseed oil,ethyl acetate, glycerol, hexylene glycol, isopropyl alcohol, methylalcohol, methylene chloride, methyl isobutyl ketone, mineral oil, peanutoil, propylene carbonate, sesame oil, water for injection, sterile waterfor injection, sterile water for irrigation, purified water); sorbents(powdered cellulose, charcoal, purified siliceous earth); carbon dioxidesorbents (barium hydroxide lime, soda lime); stiffening agents(hydrogenated castor oil, cetostearyl alcohol, cetyl alcohol, cetylesters wax, hard fat, paraffin, polyethylene excipient, stearyl alcohol,emulsifying wax, white wax, yellow wax); suspending and/orviscosity-increasing agents (acacia, agar, alginic acid, aluminummonostearate, bentonite, purified bentonite, magma bentonite, carbomer,carboxymethylcellulose calcium, carboxymethylcellulose sodium,carboxymethylcellulose sodium carrageenan, microcrystalline andcarboxymethylcellulose sodium cellulose, dextrin, gelatin, guar gum,hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethylcellulose, magnesium aluminum silicate, methylcellulose, pectin,polyethylene oxide, polyvinyl alcohol, povidone, alginate, silicondioxide, colloidal silicon dioxide, sodium alginate, tragacanth, xanthangum); sweetening agents (aspartame, dextrates, dextrose, excipientdextrose, fructose, mannitol, saccharin, calcium saccharin, sodiumsaccharin, sorbitol, solution sorbitol, sucrose, compressible sugar,confectioner's sugar, syrup); surfactants (simethicone); tablet binders(acacia, alginic acid, sodium carboxymethylcellulose, microcrystallinecellulose, dextrin, ethylcellulose, gelatin, liquid glucose, guar gum,hydroxypropyl methylcellulose, methylcellulose, polyethylene oxide,povidone, pregelatinized starch, syrup); tablet and/or capsule diluents(calcium carbonate, dibasic calcium phosphate, tribasic calciumphosphate, calcium sulfate, microcrystalline cellulose, powderedcellulose, dextrates, dextrin, dextrose excipient, fructose, kaolin,lactose, mannitol, sorbitol, starch, pregelatinized starch, sucrose,compressible sugar, confectioner's sugar); tablet disintegrants (alginicacid, microcrystalline cellulose, croscarmellose sodium, crospovidone,polacrilin potassium, sodium starch glycolate, starch, pregelatinizedstarch); tablet and/or capsule lubricants (calcium stearate, glycerylbehenate, magnesium stearate, light mineral oil, sodium stearylfumarate, stearic acid, purified stearic acid, talc, hydrogenatedvegetable oil, zinc stearate); thickening agents (gelatin having a bloomstrength of 50-100); tonicity agent (dextrose, glycerol, mannitol,potassium chloride, sodium chloride); vehicle: flavored and/or sweetened(aromatic elixir, compound benzaldehyde elixir, iso-alcoholic elixir,peppermint water, sorbitol solution, syrup, tolu balsam syrup); vehicle:oleaginous (almond oil, corn oil, cottonseed oil, ethyl oleate,isopropyl myristate, isopropyl palmitate, mineral oil, light mineraloil, myristyl alcohol, octyl dodecanol, olive oil, peanut oil, persicoil, sesame oil, soybean oil, squalane); vehicle: solid carrier (sugarspheres); vehicle: sterile (bacteriostatic water for injection,bacteriostatic sodium chloride injection); viscosity-increasing (seesuspending agent); water repelling agents (cyclomethicone, dimethicone,simethicone); and/or solubilizing agent (benzalkonium chloride,benzethonium chloride, cetylpyridinium chloride, docusate sodium,nonoxynol 9, nonoxynol 10, octoxynol 9, poloxamer, polyoxyl 35 castoroil, polyoxyl 40, hydrogenated castor oil, polyoxyl 50 stearate,polyoxyl 10 oleyl ether, polyoxyl 20, cetostearyl ether, polyoxyl 40stearate, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate80, sodium lauryl sulfate, sorbitan monolaurate, sorbitan monooleate,sorbitan monopalmitate, sorbitan monostearate, tyloxapol). This list isnot meant to be exclusive, but instead merely representative of theclasses of excipients and the particular excipients that may be used inoral dosage forms as described herein.

Another embodiment is methods for manufacturing a dosing form fortreating, ameliorating, mitigating, alleviating, reducing and curing anerve damage from neurotoxic virus infection comprising: formulating acomposition into a dosage form comprising sprays, capsules, tablets,elixirs, emulsions, lozenges, suspensions, syrups, pills, lotions,epidermal patches, suppositories, inhalers, or injectables. Any methodsknown to the art for formulating extracts or active principalingredients into lotions, soaps, etc. may be utilized.

Using blue light stimulation in the 280-400 nm wavelength range,precursor molecules to psilocybin and psilocin production can beelicited from the mycelium, primordia or fruitbodies of psilocybian ortheir close non-psilocybian relatives, to induce the formation ofneurogenic compounds, including those that are not illegal, andtherefore would not violate statutes in the United States or othercountries. The goal here is to employ legal neurogenic precursor,congener or analog compounds related to psilocybin and psilocin.

Induction of bioactive compounds from mycelium through light stimulationis a method that can be used for discovering synergistic neurogeniccompounds. Blue light activates shikimic acid production in mycelium,and antioxidant polyphenols, while also stimulating tyrosinase leadingto melanization while inhibiting laccase and other enzymatic pathways,simultaneously inducing the production of psilocin, psilocybin and othertryptamines from mycelium in psilocybin active mushrooms and theirrelatives. Modifying the wavelength (i.e. blue light for 12 hours, redlight for 12 hours, per day) and frequency of light exposure, including“pulsing” of the light, can help articulate the expression of activeneurogenic ingredients. The shikimic acid pathway gives rise to aromaticamino acids (phenylalanine, tyrosine and tryptophan), which areprecursors for the formation of ergot alkaloids, lysergic acid,psilocybin and psilocin (Isaac, Fungal-Plant Interactions, SpringerNetherlands, 1992). The inventor postulates that light stimulationevoking the transformation of ergosterol to vitamin D will alsoinfluence the pathways where light induces neurogenic compounds frommycelium. These pathways are interrelated and can be used for creatingmedically significant novel compositions whose synergy is useful forrepairing the neuropathic damage by promoting neurogenesis and synapticintegrations. Exposure of mycelium to select wavelengths of light,especially blue and red spectra, may induce indole alkaloids related topsilocin analogues that have distinct antiviral and neuroprotectiveproperties.

The biosynthesis of psilocybin from tryptophan involves enzymaticdecarboxylation, methylation at the N9 position, 4-hydroxylation andO-phosphorylation. Light stimulation triggers the production ofpsilocybin and psilocin in the mycelium of, for instance Psilocybeazurescers, Psilocybe cyanescens and Psilocybe cubensis, possibly bystimulation of the enzymatic reactions. The “off/on” production ofpsilocybin, psilocin, baeocystin (the N-demethylated analog ofpsilocybin, 4-phosphoryloxy-N-methyltryptamine), norbaeocystin (theN-demethylated analog of psilocin, 4-phosphoryloxy-tryptamine) and otherassociated alkaloids from the mycelium caused by light exposure(particularly UV) are interrelated to the production of p-coumaric acidand the resultant metabolic expression of tyrosinase coding for melanin,especially prior to, during and after the time of primordia formation.The transition of the mycelium upon controlled light exposure,especially blue and UV light in the 280-420 nanometers ranges, affordsthe development of a customized suite of active ingredients, from whichan extract be created or combined with active pharmacological moleculesfor a net benefit for the patient that consumes this unique combination.

Compositions and methods utilizing combinations of psilocin orpsilocybin, and their immediate precursors, derived from mycelium thatis exposed to light, particularly in the blue spectrum, additionallycombined with erinacines or hericenones, with or without the addition ofniacin, can result in medically significant, deliverable formulationsfor human consumption supporting neurogenesis.

This inventor reported Psilocybe azurescens to be the most potentpsilocybian mushrooms in the world. (Stamets, P., Psilocybin Mushroomsof the World, 1996, Ten Speed Press.) A common side effect of takingthis psychoactive mushroom species is loss of coordination and in someoccasions, temporary paralysis. This mushroom contains ingredientsrelated to psilocybin that may swamp receptor fields to cause theseconditions. In medicine, the difference between a toxin and a medicineis often the dose. As such, this inventor suggests that other potentneurologically active ingredients are within Psilocybe azurescens (andto a lesser degree, Psilocybe cyanescens and Psilocybe subaeruginosa),which are likely useful for neurogenesis when presented or isolated atproper dosages.

Exposing mycelium grown on rice to blue and ultraviolet light in the280-420 nanometer wavelengths, for a short window of time, lasting for ashort duration of only 1-5 days, can help create and potentiate theneuroregenerative agents described herein. The intensity of light canrange from 50-1,000 lux. By incubating the sterilized rice beingactively colonized by the mycelium in plastic bags, which have grown outfor a minimum of 1 week and up to 16 weeks, UV light exposure lights canbe placed directly above and below horizontally shaped bags for maximumlight exposure. The plastic bags or glass vessels can be selected forallowing these blue light wavelengths to reach the mycelium. Themycelium can undergo a phase-change in response to light stimuli intoproducing derivative neuroregenerative agents (it is to be expected thatduring this transitional period, the mycelium may contain varyingmixtures of active compounds). This method and derivative improvementscan potentiate the production of neuroregenerative molecules, some ofwhich are intermediates during the melanization pathways activated bylight exposure at specific wavelengths. This opens possibilities forcustomizing the output of specific active molecules using precisewavelengths, exposure times and intensities of light for manufacturingand potentiating production from mycelium. Lights can be pulsed and/orsequenced with varying wavelengths for exposing mycelium. The myceliumcan also be subsequently agitated to cause new growth spurts, causingdifferentiation of hyphae with multiple nuclei per cell andhyper-expression of extracellular metabolites. Moreover, activemolecules may be emitted differentially over time, allowing for windowsof harvesting by washing the mycelium using cold EtOH and H₂O or othersolvents and processes known to the art of natural product extraction.

Serotonin is the fundamental neurotransmitter all animals use. Thatserotonin and psilocybin co-occur within psilocybin-containing(=“psilocybian”) mushrooms, and that psilocybin is a serotonin agonist,substituting for serotonin in the human brain and excitingneurotransmission, underscores the value of exploring these pathways forneurogenic compounds. Utilizing specific wavelengths of light—both blueand red spectra—can induce or suppress expression of these compounds,allowing customization of neurogenic compounds which can be usefulmedically. Exposure of red light spectra on maturing mycelium ofpsilocybin active mushroom species—which naturally would generatepsilocybin and psilocin in its mycelium—can be used to acquire compoundsuseful for neurogenesis.

Moreover, this unique combination of compounds can be incorporated intoother therapies with such combinations providing unique advantages formedically significant advancements in repairing neurons, removingamyloid plaques, improving mental health, including reducing depression,improving cognition, or agility, and improving overall the ecology ofconsciousness. The inventor foresees utilizing such compounds in helpingamputees activate their articulable prostheses. Such derivatives canhelp the improve cyborg technologies, allowing for neurons to grow intoand mesh computer interfaces.

Moreover, the production of active principle ingredients from myceliumcan be additionally enhanced by vibrational actions, including but notlimited to pulsed sonic vibration—sonification—in combination withactive principal ingredients stimulating UV wavelengths. Specific UVspectra and vibrations can be customized for enhancing yields.

Psilocybin dephosphorylates into psilocin in the liver, which thenpasses through the blood-brain barrier. Subsequent to enzymaticconversion and liver metabolism, psilocin is further degraded along atleast one pathway, one rendition of which is featured below. Thesederivative compounds have neurogenic potential and are anticipated to beuseful in nootropic formulations.

Moreover, since psilocin and its analogs are neurotransmitters, andsubstitute for serotonin, acting as an agonist exciting serotoninreceptors, their ability to enhance neurotransmission while incombination with nerve growth factors such as erinacines andhericenones, provides a unique opportunity for spurring neurogenesis.When combined with niacin, which causes nerve ending excitement, andadditionally combined with mushroom and plant extracts, compoundedneurogenic benefits are anticipated by this inventor.

The inventor claims rights to obvious embodiments of this invention,including using delivery systems, compositions, combinations and solventextraction methods as outlined in this author's previous patents andpatent applications, which are a matter of record at the United StatesPatent and Trademark Office as well as methods and compositions known tothe art of pharmaceutical science and drug discovery.

It will be apparent to one of ordinary skill in the relevant art thatsuitable modifications and adaptations to the compositions,formulations, methods, processes, and applications described herein canbe made without departing from the scope of any embodiments or aspectsthereof. The compositions and methods provided are exemplary and are notintended to limit the scope of any of the specified embodiments. All ofthe various embodiments, aspects, and options disclosed herein can becombined in any and all variations or iterations. The scope of thecompositions, formulations, methods, and processes described hereininclude all actual or potential combinations of embodiments, aspects,options, examples, and preferences herein described. The exemplarycompositions and formulations described herein may omit any component,substitute any component disclosed herein, or include any componentdisclosed elsewhere herein. The ratios of the mass of any component ofany of the compositions or formulations disclosed herein to the mass ofany other component in the formulation or to the total mass of the othercomponents in the formulation are hereby disclosed as if they wereexpressly disclosed. Should the meaning of any terms in any of thepatents or publications incorporated by reference conflict with themeaning of the terms used in this disclosure, the meanings of the termsor phrases in this disclosure are controlling. Furthermore, theforegoing discussion discloses and describes merely exemplaryembodiments. All patents and publications cited herein are incorporatedby reference herein for the specific teachings thereof.

No limitations with respect to the specific embodiments and examplesdisclosed herein are intended or should be inferred, as the examples andembodiments are representative only. While examples and preferredembodiments of the present invention have been shown and described, itwill be apparent to those skilled in the art, or ascertainable using nomore than routine experimentation, that many changes and modificationsmay be made without departing from the invention in its broader aspects.The appended claims are therefore intended to cover all such changes,modifications and equivalents as fall within the true spirit and scopeof the invention.

The invention claimed is:
 1. A pharmaceutical formulation comprising of:0.1 mg to 10 mg of psilocybin or psilocin; and an extract of Hericiumerinaceus comprising 0.1 mg to 200 mg of erinacines or hericenones. 2.The formulation of claim 1, further comprising 1 mg to 50 mg of niacin.3. The formulation of claim 1, further comprising one or morepharmaceutically acceptable excipients selected from acidifying agents,alkalizing agents, buffering agents, antimicrobial preservatives,antioxidants, or tablet disintegrants.
 4. The formulation of claim 1,further comprising extracts of Bacopa monnieri, Centella asiatica,Gingko biloba, Zingiber officinale, Ocimum sanctum, Polygonum cuspidatum, Origanum vulgare, Origanum onites, Rosmarinus officinalis,Rosmarinus eriocalyx, Curcuma longa, Camellia sinensis, Lavandulaspecies, Scutellaria lateriflora, Avena sativa and Avena byzantine,Salvia divinorum, Banisteriopsis caapi, Psychotria species, Tabemantheiboga, Voacanga africana, Tabemaemontana undulate, Ipomoea tricolor,Argyreia nervosa, Cannabis sativa, Cannabis indica, Cannabis ruderalis,or combinations thereof.
 5. The formulation of claim 1, furthercomprising one or more of: mycelia, fruitbodies, mycelial extracts, orfruitbody extracts of fungi selected from Antrodia, Beauveria,Copelandia, Cordyceps, Ganoderma, Grifola, Hericium, Inonotus, Isaria,Panaeolus, Phellinus, or combinations thereof.
 6. A pharmaceuticalformulation comprising of: 0.1 mg to 10 mg of psilocybin or psilocin; anextract of Hericium erinaceus comprising 0.1 mg to 200 mg of erinacinesor hericenones; and 1 mg to 50 mg of niacin.
 7. The formulation of claim6, further comprising one or more pharmaceutically acceptable excipientsselected from acidifying agents, alkalizing agents, buffering agents,antimicrobial preservatives, antioxidants, or tablet disintegrants. 8.The formulation of claim 6, further comprising extracts of Bacopamonnieri, Centella asiatica, Gingko biloba, Zingiber officinale, Ocimumsanctum, Polygonum cuspid atum, Origanum vulgare, Origanum onites,Rosmarinus officinalis, Rosmarinus eriocalyx, Curcuma longa, Camelliasinensis, Lavandula species, Scutellaria lateriflora, Avena sativa andAvena byzantine, Salvia divinorum, Banisteriopsis caapi, Psychotriaspecies, Tabemanthe iboga, Voacanga africana, Tabemaemontana undulate,Ipomoea tricolor, Argyreia nervosa, Cannabis sativa, Cannabis indica,Cannabis ruderalis, or combinations thereof.
 9. The formulation of claim6, further comprising one or more of: mycelia, fruitbodies, mycelialextracts, or fruitbody extracts of fungi selected from Antrodia,Beauveria, Copelandia, Cordyceps, Ganoderma, Grifola, Hericium,Inonotus, Isaria, Panaeolus, Phellinus, or combinations thereof.
 10. Apharmaceutical formulation comprising of: 0.1 mg to 10 mg psilocybin orpsilocin; and 1 mg to 50 mg of niacin.
 11. The formulation of claim 10,further comprising an extract of Hericium erinaceus comprising 0.1 mg to200 mg of erinacines or hericenones.
 12. The formulation of claim 10,further comprising one or more pharmaceutically acceptable excipientsselected from acidifying agents, alkalizing agents, buffering agents,antimicrobial preservatives, antioxidants, or tablet disintegrants. 13.The formulation of claim 10, further comprising extracts of Bacopamonnieri, Centella asiatica, Gingko biloba, Zingiber officinale, Ocimumsanctum, Polygonum cuspid atum, Origanum vulgare, Origanum onites,Rosmarinus officinalis, Rosmarinus eriocalyx, Curcuma longa, Camelliasinensis, Lavandula species, Scutellaria lateriflora, Avena sativa andAvena byzantine, Salvia divinorum, Banisteriopsis caapi, Psychotriaspecies, Tabemanthe iboga, Voacanga africana, Tabemaemontana undulate,Ipomoea tricolor, Argyreia nervosa, Cannabis sativa, Cannabis indica,Cannabis ruderalis, or combinations thereof.
 14. The formulation ofclaim 10, further comprising one or more of: mycelia, fruitbodies,mycelial extracts, or fruitbody extracts of fungi selected fromAntrodia, Beauveria, Copelandia, Cordyceps, Ganoderma, Grifola,Hericium, Inonotus, Isaria, Panaeolus, Phellinus, or combinationsthereof.
 15. A pharmaceutical dosage comprising a tablet, capsule,elixir, or suspension comprising of: 0.1 mg to 10 mg psilocybin orpsilocin; an extract of Hericium erinaceus comprising 0.1 mg to 200 mgof erinacines or hericenones; and 1 mg to 50 mg of niacin.
 16. Thedosage form of claim 15, further comprising one or more pharmaceuticallyacceptable excipients selected from acidifying agents, alkalizingagents, buffering agents, antimicrobial preservatives, antioxidants, ortablet disintegrants.
 17. The dosage form of claim 15, furthercomprising extracts of Bacopa monnieri, Centella asiatica, Gingkobiloba, Zingiber officinale, Ocimum sanctum, Polygonum cuspid atum,Origanum vulgare, Origanum onites, Rosmarinus officinalis, Rosmarinuseriocalyx, Curcuma longa, Camellia sinensis, Lavandula species,Scutellaria lateriflora, Avena sativa and Avena byzantine, Salviadivinorum, Banisteriopsis caapi, Psychotria species, Tabemanthe iboga,Voacanga africana, Tabemaemontana undulate, Ipomoea tricolor, Argyreianervosa, Cannabis sativa, Cannabis indica, Cannabis ruderalis, orcombinations thereof.
 18. The dosage form of claim 15, furthercomprising one or more of: mycelia, fruitbodies, mycelial extracts, orfruitbody extracts of fungi selected from Antrodia, Beauveria,Copelandia, Cordyceps, Ganoderma, Grifola, Hericium, Inonotus, Isaria,Panaeolus, Phellinus, or combinations thereof.